GENERAL AND CARDIAC TOXICITY OF DOXORUBICIN-LOADED GELATIN NANOPARTICLES

General and cardiac toxicity of doxorubicin loaded gelatin nanoparticl es cross-linked by glutaraldheyde were investigated in healthy rats. T he rats were treated with free doxorubicin (DXR), unloaded nanoparticl es (UNp), physical mixture of doxorubicin, and unloaded nanoparticles (DRX/UNp), and DXR-loaded nanoparticles (DXR-Np). Each group of animal s received the same dose of DXR (3 mg/kg) via i.p. once a week. Both e lectrocardiogram (EGG) parameters and body weight were measured 24h be fore each administration. Rats treated with UNp behaved as controls. D XR/UNp provoked the same toxic effects as free DXR. On the contrary, D XR-Np resulted more toxic since significant variations of both the bod y weight and the ECG parameters were observed during the first week of treatment. In addition, the rats treated with DXR-Np died between the 3(rd) and the 5(th) day after the 2(nd) administration. These results demonstrate that, in these experimental conditions, the couplage of D XR to nanoparticles enhanced the cardiotoxicity of the drug. Since DXR was linked to the protein matrix of nanoparticles via glutaraldehyde, the high toxicity of DXR-loaded nanoparticles could be due to the cov alent binding of the drug to the carrier.